Objective

This study examined the association of proximal femur shape with ipsilateral medial and lateral compartment knee osteoarthritis (OA).

Design

Radiographs were obtained from the NIH-funded Osteoarthritis Initiative (OAI). Cases of isolated radiographic lateral compartment knee OA were defined on baseline radiographs as Kellgren/Lawrence (K/L) Grade ≥ 2 and joint space narrowing (JSN) > 0 in the lateral compartment and JSN = 0 in the medial compartment; isolated medial compartment knee OA had K/L ≥ 2 and JSN > 0 medially with JSN = 0 in the lateral compartment. Controls had K/L < 2 and JSN = 0 in both compartments. Controls were frequency matched to cases by sex and 10-year age intervals. We characterized the shape of the proximal femurs on radiographs using Active Shape Modeling (ASM) and determined the association of proximal femur shape with knee OA using logistic regression.

Results

There were 168 lateral compartment knee OA cases (mean body mass index (BMI) 29.72 ± 5.26), 169 medial compartment knee OA cases (mean BMI 29.68 ± 4.83) and 168 controls (mean BMI 26.87 ± 4.2). Thirteen modes were derived for femur shape which described 95.5% of the total variance in proximal femur shape in the population. Modes 6, 8 and 12 were associated with prevalent lateral compartment knee OA. Medial compartment knee OA was associated with proximal femur modes 1, 5, 8, and 12.

Conclusions

Prevalent lateral and medial compartment knee OA are associated with different ipsilateral proximal femur shapes. Additional studies are needed to better define how the shape of the proximal femur influences compartment-specific knee OA.

Background: It has been reported that rs4446909, a single nucleotide polymorphism (SNP) in the promoter of acetylserotonin methyltransferase (ASMT), influences the expression of the ASMT enzyme. The common G allele is associated with lower ASMT activity, and therefore, diminishes conversion of N-acetylserotonin to melatonin. The G allele was associated with recurrent depressive disorder in a Polish group. ASMT might also affect bipolar relapse, given evidence that N-acetylserotonin might stimulate TRKB receptors, and TRKB may influence mood relapse in bipolar disorder. Additionally, arylalkylamine N-acetyltransferase (AANAT) polymorphisms have been reported associated with depression, perhaps through their influence upon N-acetylserotonin or melatonin synthesis.Results: To replicate and further explore these ideas, rs4446909 was genotyped in four research groups, as part of a panel of 610 SNPs surveyed by an Illumina Golden Gate assay. In 768 cases with delayed sleep phase disorder or matched controls, rs4446909 was indeed associated with the depressive symptoms on a self-report scale (P = 0.01, R2 = 0.007). However, there was no significant association of rs4446909 with self-reported depression in a sleep clinic patient group or with two groups of elderly men and women from multicenter studies, nor was the response to lithium treatment associated with rs4446909 in bipolar patients. No associations of two AANAT SNPs with depression were found.Conclusions: The evidence did not support a strong influence of rs4446909 upon mood, but the partial replication may be consistent with a modest effect. It is possible that larger or younger subject groups with improved phenotype ascertainment might demonstrate more persuasive replication. © 2011 Kripke et al; licensee BioMed Central Ltd.

Background: The epidemiology of femoroacetabular impingement (FAI) is important but incompletely understood, because most reports arise from symptomatic populations. Investigating the prevalence of FAI in a community-based cohort could help us better understand its epidemiology and in particular the degree to which it might or might not be associated with hip pain. Questions/purposes: The purposes of this study were (1) to evaluate the proportion of older (≥ 65 years of age) men with morphologic abnormalities consistent with FAI; and (2) to assess the association of the morphologic abnormalities with prevalent radiographic hip osteoarthritis (OA) and hip pain. Methods: Anteroposterior radiographs were obtained in 4140 subjects (mean age ± SD, 77 ± 5 years) from the Osteoporotic Fractures in Men study. We assessed each hip for cam, pincer, and mixed FAI types using validated radiographic definitions. Both intra- and interobserver reproducibility were > 0.9. Radiographic hip OA was assessed by an expert reader (intraobserver reproducibility, 0.7–0.8) using validated methods, and summary grades of 2 or greater (on a scale from 0 to 4) were used to define radiographic hip OA. Covariates including hip pain in the last 30 days were collected by questionnaires that were answered by all patients included in this report. Logistic regressions with generalized estimating equations were performed to evaluate the association of radiographic features of FAI and arthrosis. Results: Pincer, cam, or mixed types of radiographic FAI had a prevalence of 57% (1748 of 3053), 29% (886 of 3053), and 14% (419 of 3053), respectively, in this group of older men. Both pincer and mixed types of FAI were associated with arthrosis but not with hip pain (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.25–2.13; p < 0.001 for pincer and OR, 2.49; 95% CI, 1.65–3.76; p < 0.001 for mixed type). Patients with hips characterized by cam-type FAI had slightly reduced hip pain without the presence of arthrosis compared with hips without FAI (OR, 0.82; 95% CI, 0.68–0.99; p = 0.037). A center-edge angle > 39° and a caput-collum-diaphyseal angle < 125° were associated with arthrosis (OR, 1.53; 95% CI, 1.22–1.94; p < 0.001 and OR, 2.09; 95% CI, 1.24–3.51; p = 0.006, respectively), but not with hip pain (OR, 0.89; 95% CI, 0.77–1.03; p < 0.108 and OR, 0.99; 95% CI, 0.67–1.45; p = 0.945, respectively). An impingement angle < 70° was associated with less hip pain compared with hips with an impingement angle ≥ 70° (OR, 0.76; 95% CI, 0.61–0.95; p = 0.015). Conclusions: FAI is common in older men and represents more of an anatomic variant rather than a symptomatic disease. This finding should raise questions on how age, activities, and this anatomic variant each contribute to result in symptomatic disease. Level of Evidence: Level III, prognostic study.

Finite element model can estimate bone strength better than BMD. This study used such a model to determine its association with hip fracture risk and found that the strength estimate provided limited improvement over the hip BMDs in predicting femoral neck (FN) fracture risk only.

Introduction

Bone fractures occur only when it is loaded beyond its ultimate strength. The goal of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture as a single condition or with femoral neck (FN) and trochanter (TR) fractures separately in older men.

Methods

This prospective case-cohort study included 91 FN and 64 TR fracture cases and a random sample of 500 men (14 had a hip fracture) from the Osteoporotic Fractures in Men study during a mean ± SD follow-up of 7.7 ± 2.2 years. We analysed the baseline DXA scans of the hip using a validated plane-stress, linear-elastic FE model of the proximal femur and estimated the femoral strength during a sideways fall.

Results

The estimated strength was significantly (P < 0.05) associated with hip fracture independent of the TR and total hip (TH) BMDs but not FN BMD, and combining the strength with BMD did not improve the hip fracture prediction. The strength estimate was associated with FN fractures independent of the FN, TR and TH BMDs; the age-BMI-BMD adjusted hazard ratio (95% CI) per SD decrease of the strength was 1.68 (1.07-2.64), 2.38 (1.57, 3.61) and 2.04 (1.34, 3.11), respectively. This association with FN fracture was as strong as FN BMD (Harrell's C index for the strength 0.81 vs. FN BMD 0.81) and stronger than TR and TH BMDs (0.8 vs. 0.78 and 0.81 vs. 0.79). The strength's association with TR fracture was not independent of hip BMD.

Conclusions

Although the strength estimate provided additional information over the hip BMDs, its improvement in predictive ability over the hip BMDs was confined to FN fracture only and limited.

Objectives

The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis.

Methods

The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent.

Results

None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects.

Conclusions

Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.